a study evaluating chemotherapy with fractionated cisplatin/gemcitabine versus carboplatin/gemcitabine in the treatment of advanced or metastatic urothelial cancer with impaired renal function.

Conditions: Advanced Urothelial Cancer; Metastatic Urothelial Cancer

Summary: this is a phase ii/iii, multicenter, randomized study which includes 420 patients on six years + 3 years follow up. 92 patients will be included during the phase ii ; additional 328 patients will be included. patients with an advanced or metastatic urothelial cancer with impaired renal function will be randomized in one of the two following chemotherapy arm: * fractionated cisplatin + gemcitabine. * carboplatin + gemcitabine. the main objective of the part ii study will be to evaluate the efficacy and the safety of a chemotherapy with a doublet platinum salt compound/gemcitabine with fractionated cisplatin or carboplatin in this population. the main objective of the part iii study will be to compare the efficacy in terms of overall survival of a chemotherapy with a doublet platinum salt/gemcitabine with fractionated cisplatin or carboplatin in this population.


Eligibility criteria:
inclusion criteria: 1. . age \< or = 18 years, patients aged 75 years or more will benefit from a geriatric assessment. 2. . advanced or metastatic urothelial cancer confirmed histologically or cytologically. 3. . patients liable to receive a first -line chemotherapy for advanced or metastatic urothelial carcinoma. 4. . measurable disease according to recist criteria v1.1. 5. . patients who received neoadjuvant or adjuvant chemotherapy based on platinum salt must have completed treatment at least 6 months before entering the study. 6. . performance status \< or = 2. 7. . life expectancy \> 3 months. 8. . patients with creatinine clearance between 40 and 60 ml / min ( according to cockcroft and gault ). 9. . patients having no contra-indication to overhydration. 10. . satisfactory hematological tests: neutrophils \> 1.5 g / l platelets \> 150 g / l , hemoglobin ≥ 10 g / dl. 11. . satisfactory liver function tests: total bilirubin \< 1.5 x uln (upper limit of normal), ast (aspartate aminotransferase) and alt (alanine aminotransferase)\<or = 2.5 x uln (or 5 x uln if liver metastases). 12. . in case of prior radiotherapy, a minimum of 14 days must relapse between the end of radiotherapy and study entry. 13. . for women of childbearing age , use an effective contraceptive method to study entry and for the duration of the study and 6 months after the last dose of study treatment ; for sexually active fertile men having a partner of childbearing age using effective contraception for the duration of the study and 6 months after the last dose of study treatment. 14. . patient affiliated to a social security system in france. 15. . patient signed informed consent before inclusion in the study and before any specific procedure for the study. exclusion criteria: 1. . any concomitant or previous malignancy within 5 years prior to the study ( with the exception of basal cell or squamous cell carcinoma in situ). 2. . pregnant or lactating women. 3. . patients with brain metastases or meningeal or symptoms suggestive of such secondary locations. 4. . bisphosphonate or denosumab treatment initiated within 28 days prior to randomization into the study or patient who have started such treatment during the study ( a bisphosphonate or denosumab treatment initiated within a period longer than 28 days before randomization may be continued without change during the study ). 5. . other concomitant cancer (radiation therapy, radiopharmaceutical agent chemotherapy). 6. . patients with uncontrolled infection. 7. . patients with peripheral neuropathy grade\> 1, whatever the origin or patients with hearing loss. 8. . patient with unstable disease (eg: unstable diabetes, poorly controlled hypertension , congestive heart failure or myocardial infarction within 3 months prior to study entry). 9. . known hypersensitivity to study drugs. 10. . treatment with any other investigational drug within 30 days before inclusion. 11. . any psychological condition , familial, sociological or geographical not to comply with medical monitoring and / or procedures in the study protocol. 12. . patient protected by law.

Keywords: urothelial cancer, renal function impaired.